Discussion

The work contained in this thesis reflects our efforts to better understand the complex interplay between mental health, genetics, and the brain functional connectome. We compared the results from our analyses in the UKB with publicly available GWAS summary statistics on a number of psychiatric disorders. The work was divided up into three projects which each culminated in a scientific paper.

Firstly, we identified widespread genetic correlation between phenotypically independent symtpom profiles relevant for mental health in an undiagnosed population sample. We also found that the genetic correlation with psychiatric disorders was usually stronger for independent components whose construct most closely resembled the symptoms in the psychiatric disorders. Secondly, the shared genetic architecture between multimodal features extended also to the brain functional connectome, showing meaningful shared genetic loci with psychiatric disorders (mainly SCZ). These shared genetic loci were associated with a number of relevant neurobiological processes, such as synaptic functioning and cell signaling. Finally, we characterized the shared genetic architecture between the brain functional connectome and the symptom profiles idenfied in the first project.

In this chapter:

• Main findings
• Ethical considerations
• Methodological considerations
• Implications for future research